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      Biocontainment through Reengineered Genetic Codes

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      ChemBioChem

      Wiley-Blackwell

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          Abstract

          It's only unnatural: Reengineered genetic codes can achieve biocontainment by specifying different meanings for protein sequences in modified versus natural organisms; the synthetic bacterium discussed here is dependent on unnatural amino acids because its reengineered genetic code specifies unnatural amino acids in essential genes.

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          Most cited references 6

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          Adding new chemistries to the genetic code.

          The development of new orthogonal aminoacyl-tRNA synthetase/tRNA pairs has led to the addition of approximately 70 unnatural amino acids (UAAs) to the genetic codes of Escherichia coli, yeast, and mammalian cells. These UAAs represent a wide range of structures and functions not found in the canonical 20 amino acids and thus provide new opportunities to generate proteins with enhanced or novel properties and probes of protein structure and function.
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            A network of orthogonal ribosome x mRNA pairs.

            Synthetic biology promises the ability to program cells with new functions. Simple oscillators, switches, logic functions, cell-cell communication and pattern-forming circuits have been created by the connection of a small set of natural transcription factors and their binding sites in different ways to produce different networks of molecular interactions. However, the controlled synthesis of more complex synthetic networks and functions will require an expanded set of functional molecules with known molecular specificities. Here, we tailored the molecular specificity of duplicated Escherichia coli ribosome x mRNA pairs with respect to the wild-type ribosome and mRNAs to produce multiple orthogonal ribosome x orthogonal mRNA pairs that can process information in parallel with, but independent of, their wild-type progenitors. In these pairs, the ribosome exclusively translates the orthogonal mRNA, and the orthogonal mRNA is not a substrate for cellular ribosomes. We predicted and measured the network of interactions between orthogonal ribosomes and orthogonal mRNAs, and showed that they can be used to post-transcriptionally program the cell with Boolean logic.
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              Preparing synthetic biology for the world

              Synthetic Biology promises low-cost, exponentially scalable products and global health solutions in the form of self-replicating organisms, or “living devices.” As these promises are realized, proof-of-concept systems will gradually migrate from tightly regulated laboratory or industrial environments into private spaces as, for instance, probiotic health products, food, and even do-it-yourself bioengineered systems. What additional steps, if any, should be taken before releasing engineered self-replicating organisms into a broader user space? In this review, we explain how studies of genetically modified organisms lay groundwork for the future landscape of biosafety. Early in the design process, biological engineers are anticipating potential hazards and developing innovative tools to mitigate risk. Here, we survey lessons learned, ongoing efforts to engineer intrinsic biocontainment, and how different stakeholders in synthetic biology can act to accomplish best practices for biosafety.
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                Author and article information

                Journal
                ChemBioChem
                ChemBioChem
                Wiley-Blackwell
                14394227
                May 26 2015
                May 26 2015
                : 16
                : 8
                : 1149-1151
                Article
                10.1002/cbic.201500157
                25917937
                © 2015
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